Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats

Giordano de Guglielmo, Marsida Kallupi, Matthew B. Pomrenze, Elena Crawford, Sierra Simpson, Paul Schweitzer, George F. Koob, Robert O Messing, Olivier George

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The activation of a neuronal ensemble in the central nucleus of the amygdala (CeA) during alcohol withdrawal has been hypothesized to induce high levels of alcohol drinking in dependent rats. In the present study we describe that the CeA neuronal ensemble that is activated by withdrawal from chronic alcohol exposure contains ~80% corticotropin-releasing factor (CRF) neurons and that the optogenetic inactivation of these CeA CRF+ neurons prevents recruitment of the neuronal ensemble, decreases the escalation of alcohol drinking, and decreases the intensity of somatic signs of withdrawal. Optogenetic dissection of the downstream neuronal pathways demonstrates that the reversal of addiction-like behaviors is observed after the inhibition of CeA CRF projections to the bed nucleus of the stria terminalis (BNST) and that inhibition of the CRF CeA-BNST pathway is mediated by inhibition of the CRF-CRF 1 system and inhibition of BNST cell firing. These results suggest that the CRF CeA-BNST pathway could be targeted for the treatment of excessive drinking in alcohol use disorder.

Original languageEnglish (US)
Article number1238
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Corticotropin-Releasing Hormone
releasing
deactivation
rats
Rats
alcohols
Alcohols
Septal Nuclei
nuclei
Optogenetics
Alcohol Drinking
drinking
beds
Neurons
neurons
Dissection
dissection
Central Amygdaloid Nucleus
Chemical activation
projection

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

de Guglielmo, G., Kallupi, M., Pomrenze, M. B., Crawford, E., Simpson, S., Schweitzer, P., ... George, O. (2019). Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats. Nature Communications, 10(1), [1238]. https://doi.org/10.1038/s41467-019-09183-0

Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats. / de Guglielmo, Giordano; Kallupi, Marsida; Pomrenze, Matthew B.; Crawford, Elena; Simpson, Sierra; Schweitzer, Paul; Koob, George F.; Messing, Robert O; George, Olivier.

In: Nature Communications, Vol. 10, No. 1, 1238, 01.12.2019.

Research output: Contribution to journalArticle

de Guglielmo, G, Kallupi, M, Pomrenze, MB, Crawford, E, Simpson, S, Schweitzer, P, Koob, GF, Messing, RO & George, O 2019, 'Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats', Nature Communications, vol. 10, no. 1, 1238. https://doi.org/10.1038/s41467-019-09183-0
de Guglielmo, Giordano ; Kallupi, Marsida ; Pomrenze, Matthew B. ; Crawford, Elena ; Simpson, Sierra ; Schweitzer, Paul ; Koob, George F. ; Messing, Robert O ; George, Olivier. / Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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